Airway Surfactant Protein D Deficiency in Adults With Severe Asthma

• Published in: Chest Vol. 149; no. 5; p. 1165
• Main Authors: Mackay, Rose-Marie A, Grainge, Christopher L, Lau, Laurie C, Barber, Clair, Clark, Howard W, Howarth, Peter H
• Format: Journal Article
• Language: English
• Published: United States 01.05.2016
• Subjects: Adolescent; Adult; Aged; Asthma - immunology; Asthma - metabolism; Blotting, Western; Bronchoalveolar Lavage Fluid - chemistry; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Eosinophil Cationic Protein - metabolism; Female; Humans; Immunity, Innate - immunology; Leukocyte Count; Leukocyte Elastase - metabolism; Lipopolysaccharides - metabolism; Male; Middle Aged; Neutrophils; Peroxidase - metabolism; Pulmonary Surfactant-Associated Protein D - immunology; Pulmonary Surfactant-Associated Protein D - metabolism; Severity of Illness Index; Young Adult; biomarkers; severe asthma; neutrophilic inflammation; asthma; eosinophilic inflammation; bronchoalveolar lavage; immunology (lung); surfactant protein D; immunology asthma
• ISSN: 1931-3543
• DOI: 10.1016/j.chest.2015.11.012

Surfactant protein D (SP-D) is an essential component of the innate immune defense against pathogens within the airways. SP-D also regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma. SP-D concentrations were measured in matched serum and BAL samples collected from 10 healthy control subjects (HC) and 50 patients with asthma (22 with mild asthma [MA] and 28 with severe asthma [SA]). These samples were also evaluated by using Western blot analysis to investigate variations in SP-D size. SP-D levels in BAL samples were significantly lower in SA compared with HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein concentrations in SA (P < .01). Serum SP-D was significantly increased in SA compared with HC and MA (P < .001), and BAL/serum ratios were significantly lower in SA compared with HC and MA (P < .001). Reduced SP-D levels in BAL samples, with concomitant increases in serum in SA, were associated with degraded fragments of SP-D in the serum and increased BAL neutrophil counts and lipopolysaccharide levels. These findings suggest defective innate immunity within the airways in SA, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in patients with SA may provide a peripheral blood biomarker, reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways.